RESUMEN
Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.
Asunto(s)
Biomarcadores , Gripe Humana , Interleucina-15 , Interleucina-8 , Humanos , Gripe Humana/inmunología , Gripe Humana/sangre , Masculino , Femenino , Biomarcadores/sangre , Pronóstico , Persona de Mediana Edad , Interleucina-15/sangre , Anciano , Estudios Prospectivos , Interleucina-8/sangre , AdultoRESUMEN
[This corrects the article DOI: 10.3389/fimmu.2024.1443096.].
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Biomarcadores , Gripe Humana , Interleucina-15 , Interleucina-8 , Humanos , Gripe Humana/inmunología , Gripe Humana/complicaciones , Pronóstico , Interleucina-8/sangreRESUMEN
Two different single nucleotide substitutions in intron 2 give rise to novel HLA-DQB1*03:02:01 alleles.
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Alelos , Cadenas beta de HLA-DQ , Intrones , Humanos , Prueba de Histocompatibilidad , Cadenas beta de HLA-DQ/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Two nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-B*35:01:01:39 and -B*35:03:01:32.
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Genes MHC Clase I , Antígenos HLA-B , Humanos , Alelos , Antígenos HLA-B/genética , Intrones , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Three nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-DQB1*03:01:01:54, -DQB1*03:01:01:56, -DQB1*03:01:01:58.
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Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas beta de HLA-DQ/genética , IntronesRESUMEN
Seven different single nucleotide substitutions in non-coding regions gave rise to novel HLA-DPA1*01:03:01 variants.
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Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , Prueba de HistocompatibilidadRESUMEN
Characterization by next-generation sequencing of four novel HLA alleles: C*17:03:01:07, C*16:01:01:39, B*15:17:01:07, and B*44:03:01:57.
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Secuenciación de Nucleótidos de Alto Rendimiento , Nucleótidos , Humanos , Regiones no Traducidas 3' , AlelosRESUMEN
HLA-DPA1*02:01:25 differs from DPA1*02:01:01:02 by a synonymous transition in exon 2.
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Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , Exones/genéticaRESUMEN
HLA-DQA1*05:71, the first HLA-DQA1 allele with Aspartic Acid at residue 208 in the transmembrane domain.
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Ácido Aspártico , Humanos , Ácido Aspártico/genética , Alelos , Análisis de Secuencia de ADN , Cadenas alfa de HLA-DQ/genéticaRESUMEN
The novel HLA-DQB1*03:02:01:14 was likely generated by a recombination event between DQB1*03:02:01:01 and DQB1*03:03:02:01.
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Secuenciación de Nucleótidos de Alto Rendimiento , Recombinación Genética , Humanos , Alelos , Cadenas beta de HLA-DQ/genéticaRESUMEN
Two transitions in intronic regions give rise to the novel alleles: HLA-DQB1*05:02:01:13 and HLA-DQB1*05:02:01:14.
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Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas beta de HLA-DQ/genética , IntronesRESUMEN
A missense nucleotide substitution in codon -17 in the leader peptide results in the novel HLA-DRB1*04:354 allele.
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Nucleótidos , Valina , Humanos , Cadenas HLA-DRB1/genética , Alelos , Valina/genética , Exones/genéticaRESUMEN
The failure to identify HLA null alleles in bone marrow transplantation could be life-threatening because this could result in an HLA mismatch with the ability to trigger the graft-vs-host disease (GVHD) and to reduce patient's survival. In this report we describe the identification and characterization of the novel HLA-DPA1*02:66:02N allele with a non-sense codon in exon 2. This new allele was discovered in two unrelated bone marrow donors during routine HLA-typing using next-generation sequencing (NGS). DPA1*02:66:02N is homologous to DPA1*02:01:01:03 with a single nucleotide difference in exon 2, codon 50, where the replacement of C located at genomic position 3825 by T, causes the formation of a premature stop codon (TGA), resulting in a null allele. This description illustrates the benefits of HLA typing by NGS since it permits to reduce ambiguities, identify new alleles, analyze multiple HLA loci and improve transplantation outcome.
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Codón sin Sentido , Cadenas alfa de HLA-DP , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , Exones/genética , Codón , Prueba de Histocompatibilidad/métodosRESUMEN
Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1ß and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.
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COVID-19 , Fallo Renal Crónico , Humanos , SARS-CoV-2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Interleucina-8 , Citocinas/metabolismo , Fallo Renal Crónico/terapia , Diálisis RenalRESUMEN
A synonymous substitution in exon 2 and intronic insertion results in the novel HLA-DQA1*01:04:07 allele.
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Antígenos HLA-DQ , Humanos , Antígenos HLA-DQ/genética , Alelos , Cadenas alfa de HLA-DQ/genética , ExonesRESUMEN
A nonsynonymous nucleotide substitution in exon 1 results in the novel HLA-DQB1*03:493 allele.
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Ácido Glutámico , Señales de Clasificación de Proteína , Humanos , Alelos , Ácido Glutámico/genética , Secuencia de Bases , Cadenas beta de HLA-DQ/genéticaRESUMEN
NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution.
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COVID-19 , Células T Asesinas Naturales , Degranulación de la Célula , Humanos , Interferón gamma/metabolismo , Células Asesinas Naturales , Activación de LinfocitosRESUMEN
The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody specificity in COVID-19 patients and to classify them according to evolution based on infection severity. A unicenter, randomized group of 146 COVID-19 patients was divided into four groups in accordance with the most critical events during the course of disease. The immunophenotype and T-helper subsets were analyzed by flow cytometry. Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Th1 immunity, with a lower Th17 and less activated T-cells at the time of sample acquisition compared not only with symptomatic patients, but also with healthy controls. Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Th1 responses and more activated T-cells. The multivariate analysis of the immunological and inflammatory parameters, together with the comorbidities, showed that the Th1 response was an independent protective factor for the prevention of hospitalization (OR 0.17, 95% CI 0.03-0.81), with an AUC of 0.844. Likewise, the Th1 response was found to be an independent protective factor for severe forms of the disease (OR 0.09, 95% CI: 0.01-0.63, p = 0.015, AUC: 0.873). In conclusion, a predominant Th1 immune response in the acute phase of the SARS-CoV-2 infection could be used as a tool to identify patients who might have a good disease evolution.